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J. Cell Biol. 178 (3): 355-361

Copyright © 2007 by the Rockefeller University Press.

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Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity

Karni Schlessinger1, Edward J. McManus2, , and Alan Hall1

1 Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group and Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, England, UK
2 Medical Research Council Protein Phosphorylation Unit, University of Dundee, Dundee DD2 5DQ, Scotland, UK

Correspondence to Alan Hall: halla{at}mskcc.org

Abstract: Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We previously reported that centrosomal reorientation and microtubule polarization depend on a Cdc42-regulated signal transduction pathway involving activation of the Par6/aPKC complex followed by inhibition of GSK-3ß and accumulation of the adenomatous polyposis coli (APC) protein at the plus ends of leading-edge microtubules. Using monolayers of primary rodent embryo fibroblasts, we show here that dishevelled (Dvl) and axin, two major components of the Wnt signaling pathway are required for centrosome reorientation and that Wnt5a is required for activation of this pathway. We conclude that disruption of cell–cell contacts leads to the activation of a noncanonical Wnt/dishevelled signal transduction pathway that cooperates with Cdc42/Par6/aPKC to promote polarized reorganization of the microtubule cytoskeleton.

E.J. McManus' present address is Division of Molecular Medicine, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

A. Hall's present address is Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Abbreviations used in this paper: APC, adenomatous polyposis coli; aPKC, atypical protein kinase C; Dkk1, Dickkopf 1; Dvl, Dishevelled; MEF, mouse embryonic fibroblasts; REF, rat embryonic fibroblasts; sFRP1, soluble frizzled related protein 1.

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